PXD013414 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Role of ATR in mitochondrial functions and metabolism |
Description | The PIKK superfamily member ATR is a key factor in DNA damage response (DDR) and is vital for the maintenance of genomic stability. DNA single strand breaks (SSBs) and replication stress activate ATR to phosphorylate a wide range of downstream substrates, which activates cell cycle checkpoint, senescence induction, cell death, and R-loop disintegration. ATR mutation causes the human ATR-Seckel syndrome, characterized by dwarfism, microcephaly and intellectual disabilities. Recent studies have implied ATR in non-nuclear functions; however, ATR's function in mitochondrial metabolism and a link to human diseases remains largely unknown. Here we show that ATR is located in mitochondria and its deletion alters mitochondrial dynamics prior to the DDR. ATR deletion disturbs the electron transfer chain (ETC) resulting in ROS overproduction and switches energy production from OXPHOS to the TCA cycle. Multi-omics analyses together with biochemical studies showed an imbalance of ETC proteins and membrane lipids accompanied with a dysregulation of key metabolic signaling pathways, including AMPK, mTOR and PGC1α. Pharmacological intervention of AMPK signaling or ETC functions delineates the metabolic pathways affected in ATR deleted cells. Mitochondrial metabolic dysfunction is more pronounced in ATR deleted neural cells and brain tissues, implicating a connection with neuropathological processes. Thus, ATR plays, beyond its well-known DDR function, an important role for cell metabolism and mitochondrial functionality, which contributes to the manifestation of neuronal deficit of ATR-Seckel. |
HostingRepository | PRIDE |
AnnounceDate | 2021-05-05 |
AnnouncementXML | Submission_2021-07-20_00:49:50.664.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Joanna Kirkpatrick |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2019-04-09 01:59:33 | ID requested | |
1 | 2021-05-04 22:14:14 | announced | |
⏵ 2 | 2021-07-20 00:49:52 | announced | 2021-07-20: Updated publication reference for PubMed record(s): 34210973. |
Publication List
Kirtay M, Sell J, Marx C, Haselmann H, Ceanga M, Zhou ZW, Rahmati V, Kirkpatrick J, Buder K, Grigaravicius P, Ori A, Geis C, Wang ZQ, ATR regulates neuronal activity by modulating presynaptic firing. Nat Commun, 12(1):4067(2021) [pubmed] |
Keyword List
curator keyword: Biological |
submitter keyword: ATR, mitochondrial function, metabolism |
Contact List
Zhao-Qi Wang |
contact affiliation | Leibniz Institute on Aging – Fritz Lipmann Institute (FLI) Beutenbergstrasse 11 07745 Jena, Germany |
contact email | Zhao-Qi.Wang@leibniz-fli.de |
lab head | |
Joanna Kirkpatrick |
contact affiliation | Leibniz Institute on Aging - FLI |
contact email | joanna.kirkpatrick@leibniz-fli.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD013414
- Label: PRIDE project
- Name: Role of ATR in mitochondrial functions and metabolism